Expression of major histocompatibility complex and HIV antigens within the brains of AIDS patients

Achim, Cristian L.; Morey, Mitchel; Wiley, Clayton A.

doi:10.1097/00002030-199105000-00009

Cited by 52 publications

(20 citation statements)

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“…Our finding that the cortex was only infrequently and less severely infected compared to the deeper structures of the brain is in accord with the findings of several investigators [13,15,29,481 but contrasts with that of Gabutda and coworkers [49). The latter group, however, did not systematically sample the same areas as in the other studies and the number of samples was small.…”

Section: Cowelation Of Clinical Adc Stage With Hiv-1 Antigen Detectiosupporting

confidence: 86%

AIDS dementia complex and HIV‐1 brain infection: Clinical‐virological correlations

Brew

Rosenblum

Cronin

et al. 1995

Annals of Neurology

241

125

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To evaluate the presence and distribution of central nervous system infection by human immunodeficiency virus type 1 (HIV-1), we used immunohistochemical methods to map the HIV-1 p24 core protein in the brains of 55 autopsied patients with acquired immunodeficiency syndrome (AIDS). In a subset of 40 of these patients who had undergone antemortem neurological evaluation of the AIDS dementia complex (ADC), we analyzed the relation between the severities of the viral infection and clinical dysfunction. Viral antigen was detected in macrophages and cells with morphological and immunohistochemical characteristics of microglia as well as multinucleated cells. The distribution of antigen-positive cells preferentially involved certain deep brain structures, especially the globus pallidus, other basal ganglia nuclei, and the central white matter. Overall, the presence and frequency of infected cells were highly correlated with the histological findings of multinucleated-cell encephalitis and in general with the clinical ADC stage. However, infection was often more limited than might be "anticipated" from the severity of patients' clinical dysfunction: Only 61% of patients with at least ADC stage 1 had detectable antigen and of these only approximately 30% of the brain sections were antigen positive. These results suggest a pathogenetic model of ADC where virus- or cell-coded toxins amplify the effect of limited brain infection.

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Section: Cowelation Of Clinical Adc Stage With Hiv-1 Antigen Detectiosupporting

confidence: 86%

AIDS dementia complex and HIV‐1 brain infection: Clinical‐virological correlations

Brew

Rosenblum

Cronin

et al. 1995

Annals of Neurology

241

125

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“…First, administration of AZT has been shown to improve neurological dysfunction in AIDS patients with dementia (29,32,43). Second, quantitative decreases in immunostaining for p24 in brains of AIDS patients, at autopsy, may be associated with AZT treatment (1). Third, AZT achieves the highest CSF/plasma ratio of any nucleoside (7).…”

Section: Methodsmentioning

confidence: 99%

Effect of 3'-azido-3'-deoxythymidine on human immunodeficiency virus type 1 replication in human fetal brain macrophages

Geleziunas

Arts

Boulerice

et al. 1993

Antimicrob Agents Chemother

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We investigated whether cells derived from the fetal central nervous system can support productive infection by a human immunodeficiency virus type 1 (HIV-1) isolate termed UHC-1, produced by a cellular clone derived from HIV-1 strain HIV-IIIB chronically infected U-937 promonocytic cells, and what the effect of nucleoside analogs might be on viral replication in this system. Fractionation of human fetal brain tissue into two different populations, enriched for either astrocytes or macrophages, showed that only the latter were able to support productive UHC-1 replication and generation of detectable progeny virus. Pretreatment of fetal brain macrophages with either of two nucleoside analogs, 3'-azido-3'-deoxythymidine (AZT) or the (-) enantiomer of 2'-deoxy-3'-thiacytidine, efficiently blocked production of progeny virus. Generation of unintegrated proviral DNA and HIV-1 transcripts were inhibited by pretreatment of fetal brain macrophages with 1 microM AZT. Administration of AZT at 24 h postinfection led to a slight reduction in viral transcript levels and viral progeny production by day 15 postinfection; however, brain macrophages under these conditions did not contain detectable amounts of unintegrated viral DNA. These results suggest that AZT may interfere with the accumulation of unintegrated HIV-1 DNA in brain macrophages. This is the first demonstration that nucleoside analogs are able to block HIV-1 replication in primary cultures of brain cells.

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“…antigens in microglia which are frequently also positive for TNFa [ 137,138]. Cytokines such as TNFa may be toxic for myelin or oligodendrocytes, and could thus lead to myelin damage as observed in HIV-1-associated vac uolar myelopathy [139], As discussed before, however.…”

Section: Microglia In Aids and Opportunistic Infectionsmentioning

confidence: 99%

Surveillance, Intervention and Cytotoxicity: Is There a Protective Role of Microglia?

1994

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The study of microglial cell biology has become the key to understanding the brain''s fundamental tissue reactions as well as the cellular mechanisms underlying CNS disease. This article focuses on glial-neuronal interactions with special reference to human pathology. Three important areas of brain pathology are critically reviewed: multiple sclerosis and CNS inflammation, the brain in AIDS and opportunistic infections, and neurodegenerative disorders. Although microglial cytotoxicity may cause bystander damage, e.g. in ischemia, there is little evidence to support the view that microglial activation per se is pathogenic. Results suggesting that one important normal function of microglia is to protect the integrity of the central nervous system are discussed. The concept is proposed that microglia function as a highly developed guardian to the CNS.

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Expression of major histocompatibility complex and HIV antigens within the brains of AIDS patients

Cited by 52 publications

References 0 publications

AIDS dementia complex and HIV‐1 brain infection: Clinical‐virological correlations

AIDS dementia complex and HIV‐1 brain infection: Clinical‐virological correlations

Effect of 3'-azido-3'-deoxythymidine on human immunodeficiency virus type 1 replication in human fetal brain macrophages

Surveillance, Intervention and Cytotoxicity: Is There a Protective Role of Microglia?

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